E2A-PBX1 binds and activates genes through RUNX1-dependent and independent mechanisms. (A) E2A-PBX1 binds through RUNX1 and activates growth promoting genes, including WNT16 and RUNX1 itself. (B) E2A-PBX1 can directly bind and activate genes relevant to B-cell transformation, such as IZKF1. Although the RUNX-dependent pathway appears to be sufficient for transformation in vitro, full activity requires both mechanisms.